Leibniz-Institut für umweltmedizinische Forschung (IUF), D-40225 Düsseldorf, Germany.
Arch Biochem Biophys. 2010 Sep 1;501(1):58-64. doi: 10.1016/j.abb.2010.05.024. Epub 2010 May 27.
The green tea flavonoid epigallocatechin gallate (EGCG) is demonstrated in this study to modulate FoxO transcription factors in human skin fibroblasts in culture. EGCG at 1 microM stimulated FoxO transcription factor nuclear accumulation and DNA binding activity. This effect was masked at higher EGCG concentrations (100 microM) by EGCG-derived hydrogen peroxide generated in cell culture media that stimulates phosphoinositide-3'-kinase (PI3K)/Akt signaling to attenuate FoxO activity, involving FoxO phosphorylation, nuclear exclusion and attenuation of DNA binding activity. Like low concentrations of EGCG, harmine, an inhibitor of the FoxO kinase DYRK1a, stimulated FoxO nuclear accumulation and DNA binding activity. Exposure of Caenorhabditis elegans worms to EGCG caused nuclear accumulation of the FoxO ortholog, DAF-16, and enhanced expression of the DAF-16 target gene, sod-3. In line with the role of FoxO/DAF-16 in the control of life span, C. elegans mean and maximum life span were enhanced by 20% and 13%, respectively, by EGCG.
在这项研究中，绿茶黄酮表没食子儿茶素没食子酸酯（EGCG）被证明可以调节培养的人皮肤成纤维细胞中的 FoxO 转录因子。1 μM 的 EGCG 刺激 FoxO 转录因子核积累和 DNA 结合活性。然而，在更高的 EGCG 浓度（100 μM）下，细胞培养介质中产生的 EGCG 衍生的过氧化氢会刺激磷酯酰肌醇-3'-激酶（PI3K）/Akt 信号通路，从而减弱 FoxO 活性，涉及 FoxO 磷酸化、核排除和 DNA 结合活性的减弱。与低浓度的 EGCG 类似，FoxO 激酶 DYRK1a 的抑制剂哈梅林（harmine）刺激 FoxO 核积累和 DNA 结合活性。暴露于 EGCG 的秀丽隐杆线虫（Caenorhabditis elegans）导致 FoxO 同源物 DAF-16 的核积累，并增强了 DAF-16 靶基因 sod-3 的表达。与 FoxO/DAF-16 在控制寿命中的作用一致，EGCG 分别使秀丽隐杆线虫的平均寿命和最大寿命延长了 20%和 13%。
